Risk Assessment Report
Isotianil (2nd edition) (Pesticides)
2023 年 11 巻 4 号 p. 78-80
詳細
2023 年 11 巻 4 号 p. 78-80
Food Safety Commission of Japan (FSCJ) conducted a risk assessment of isotianil (CAS No. 224049-04-1), an isothiazole agent for induced resistance to blast disease. This evaluation was requested from Ministry of Agriculture, Forestry and Fisheries (MAFF) on the reevaluation article of Agricultural Chemicals Regulation Act. Additional information including the fate in livestock (goats and chickens) and genotoxicity, and also the list of published scientific literature were newly submitted from the MAFF. The following data were used in the assessment; fate in plants (including paddy rice and potatoes), residues in crops, fate in livestock (goats and chickens), residues in livestock products, fate in animals (rats), subacute toxicity (rats, mice and dogs), chronic toxicity (rats and dogs), carcinogenicity (rats and mice), two-generation reproductive toxicity (rats), developmental toxicity (rats and rabbits), and genotoxicity. Major adverse effects of isotianil were observed in the stomach (mucosal epithelium hyperplasia of the forestomach limiting ridge in rats), the liver (including organ weight gain), and the kidney (including chronic nephropathy). No adverse effects were observed on carcinogenicity, fertility, teratogenicity, and genotoxicity. The lowest no-observed-adverse-effect level (NOAEL) obtained from the studies described above was 2.83 mg/kg bw per day in a one-year chronic toxicity study in rats. FSCJ specified an acceptable daily intake (ADI) of 0.028 mg/kg bw per day based on the NOAEL after applying a safety factor of 100. An acute reference dose (ARfD) was judged unnecessary to be specified, based on the results of a single oral administration of isotianil and other related tests.
Food Safety Commission of Japan (FSCJ) conducted a risk assessment of isotianil (CAS No. 224049-04-1), an isothiazole agent for induced resistance to blast disease. This evaluation was requested from Ministry of Agriculture, Forestry and Fisheries (MAFF) on the reevaluation article of Agricultural Chemicals Regulation Act. Additional information including the fate in livestock (goats and chickens) and genotoxicity, and also the list of published scientific literature were newly submitted from the MAFF.
The following data were used in the assessment; fate in plants (including paddy rice and potatoes), residues in crops, fate in livestock (goats and chickens), residues in livestock products, fate in animals (rats), subacute toxicity (rats, mice and dogs), chronic toxicity (rats and dogs), carcinogenicity (rats and mice), two-generation reproductive toxicity (rats), developmental toxicity (rats and rabbits), and genotoxicity.
Major adverse effects of isotianil were observed in the stomach (mucosal epithelium hyperplasia of the forestomach limiting ridge in rats), the liver (including organ weight gain), and the kidney (including chronic nephropathy). No adverse effects were observed on carcinogenicity, fertility, teratogenicity, and genotoxicity.
Based on these results, parent isotianil only was identified as the relevant substance for the residue definition for dietary risk assessment in agricultural products, livestock products and fishery products.
The lowest no-observed-adverse-effect level (NOAEL) obtained from the studies described above was 2.83 mg/kg bw per day in a one-year chronic toxicity study in rats. FSCJ specified an acceptable daily intake (ADI) of 0.028 mg/kg bw per day based on the NOAEL after applying a safety factor of 100.
An acute reference dose (ARfD) was judged unnecessary to be specified, based on the results of a single oral administration of isotianil and other related tests.
| Species | Study | Dose (mg/kg bw per day) |
NOAEL (mg/kg bw per day) |
LOAEL (mg/kg bw per day) |
Critical endpoints1) |
| Rat | 90-day subacute toxicity study |
0, 20, 500, 2 500, 20 000 ppm |
M: 29.7 F: 35.1 |
M: 148 F: 178 |
M/F: Increased T.Chol levels, etc. |
| M: 0, 1.18, 29.7, 148, 1 240 F: 0, 1.39, 35.1, 178, 1 400 |
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| One-year chronic toxicity study | 0, 60, 600, 6 000, 20 000 ppm |
M: 2.83 F: 3.70 |
M: 27.9 F: 37.3 |
M/F: Increased T.Chol levels and increased relative weight of the liver | |
| M: 0, 2.83, 27.9 291, 979 F: 0, 3.70, 37.3, 381, 1 250 |
|||||
| Two-year carcinogenicity study |
0, 2 000, 6 000, 20 000 ppm |
M: - F: - |
M: 79.2 F: 105 |
M/F: Mucosal epithelium hyperplasia of the
forestomach limiting ridge F: Chronic nephropathy (No carcinogenicity is observed) |
|
| M: 0, 79.2, 242, 823 F: 0, 105, 311, 1 050 |
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| Two-generation reproductive toxicity study |
0, 50, 1 000, 10 000 ppm | Parent PM: 3.35 PF: 4.16 F1M: 4.05 F1F: 4.74 Offspring PM: 3.35 PF: 4.16 F1M: 4.05 F1F: 4.74 |
Parent PM: 66.8 PF: 83.9 F1M: 80.6 F1F: 95 Offspring PM: 66.8 PF: 83.9 F1M: 80.6 F1F: 95 |
Parent M/F: Increased absolute and relative weights of the liver, etc. Offspring: Low body weight (No effect on fertility is observed) |
|
| PM: 0, 3.35, 66.8, 662 PF: 0, 4.16, 83.9, 831 F1M: 0, 4.05, 80.6, 823 F1F: 0, 4.74, 95, 941 |
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| Developmental toxicity study |
0, 100, 300, 1 000 | Dams: 1 000 Fetuses: 1 000 |
Dams: - Fetuses: - |
Dams and fetuses: No toxicity (No teratogenicity observed) |
|
| Mouse | 90-day subacute toxicity study |
0, 150, 1 000, 7 000 ppm | M: 1 310 F: 2 470 |
M: - F: - |
M/F: No toxicity |
| M: 0, 33.1, 204, 1 310 F: 0, 54.8, 401, 2 470 |
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| 18-month carcinogenicity study |
0, 70, 700, 7 000 ppm | M: 706 F: 667 |
M/F: - | M/F: No toxicity (No carcinogenicity is observed) |
|
| M: 0, 6.89, 71.5, 706 F: 0, 6.66, 67.2, 667 |
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| Rabbit | Developmental toxicity study | 0, 100, 300, 1 000 | Dams: 300 Fetuses: 300 |
Dams: 1 000 Fetuses: 1 000 | Dams: Suppressed body weight gain, etc. Fetuses: Low body weight (No teratogenicity observed) |
| Dog | 90-day subacute toxicity study | 0, 500, 2 000, 8 000 ppm | M: 12.2 F: 13.4 |
M: 51.1 F: 54.4 |
M/F: Increased ALT, etc. |
| M: 0, 12.2, 51.1, 200 F: 0, 13.4, 54.4, 211 |
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| One-year chronic toxicity study | 0, 200, 1 000, 5 000/3 000 ppm |
M: 5.22 F: 5.33 |
M: 27.2 F: 26.9 |
M: Increased in absolute and relative weights of
the liver, etc. F: Increase in absolute weight of the spleen, etc. |
|
| M: 0, 5.22, 27.2, 107 F: 0, 5.33, 26.9, 110 |
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| ADI | NOAEL: 2.83 SF: 100 ADI: 0.028 |
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| The critical study for setting ADI | One-year chronic toxicity study (rat) | ||||
ADI, Acceptable daily intake; ALT, Alanine aminotransferase; NOAEL, No-observed-adverse-effect level; SF, Safety factor; T. Chol, Total cholesterol; -, LOAEL could not be specified.
1) The adverse effect observed at LOAEL
FSCJ wishes to thank the members of the Expert Committee on Pesticides for preparation of the original full report1).
